Q02790 · FKBP4_HUMAN
- ProteinPeptidyl-prolyl cis-trans isomerase FKBP4
- GeneFKBP4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids459 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.
Catalytic activity
- [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
Activity regulation
Inhibited by FK506.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePeptidyl-prolyl cis-trans isomerase FKBP4
- EC number
- Short namesPPIase FKBP4
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ02790
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor (PubMed:21730050).
Colocalized with MAPT/TAU in the distal part of the primary cortical neurons (By similarity).
Colocalized with MAPT/TAU in the distal part of the primary cortical neurons (By similarity).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 67-68 | Decreased catalytic activity toward TRPC1. | ||||
Sequence: FD → DV | ||||||
Natural variant | VAR_050624 | 436 | in dbSNP:rs1042228 | |||
Sequence: T → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 470 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed; alternate | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | N-acetylmethionine; in peptidyl-prolyl cis-trans isomerase FKBP4; alternate | ||||
Sequence: M | |||||||
Chain | PRO_0000391468 | 1-459 | UniProt | Peptidyl-prolyl cis-trans isomerase FKBP4 | |||
Sequence: MTAEEMKATESGAQSAPLPMEGVDISPKQDEGVLKVIKREGTGTEMPMIGDRVFVHYTGWLLDGTKFDSSLDRKDKFSFDLGKGEVIKAWDIAIATMKVGEVCHITCKPEYAYGSAGSPPKIPPNATLVFEVELFEFKGEDLTEEEDGGIIRRIQTRGEGYAKPNEGAIVEVALEGYYKDKLFDQRELRFEIGEGENLDLPYGLERAIQRMEKGEHSIVYLKPSYAFGSVGKEKFQIPPNAELKYELHLKSFEKAKESWEMNSEEKLEQSTIVKERGTVYFKEGKYKQALLQYKKIVSWLEYESSFSNEEAQKAQALRLASHLNLAMCHLKLQAFSAAIESCNKALELDSNNEKGLFRRGEAHLAVNDFELARADFQKVLQLYPNNKAAKTQLAVCQQRIRRQLAREKKLYANMFERLAEEENKAKAEASSGDHPTDTEMKEEQKSNTAGSQSQVETEA | |||||||
Modified residue | 2 | UniProt | N-acetylthreonine; in peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; partial | ||||
Sequence: T | |||||||
Chain | PRO_0000075318 | 2-459 | UniProt | Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed | |||
Sequence: TAEEMKATESGAQSAPLPMEGVDISPKQDEGVLKVIKREGTGTEMPMIGDRVFVHYTGWLLDGTKFDSSLDRKDKFSFDLGKGEVIKAWDIAIATMKVGEVCHITCKPEYAYGSAGSPPKIPPNATLVFEVELFEFKGEDLTEEEDGGIIRRIQTRGEGYAKPNEGAIVEVALEGYYKDKLFDQRELRFEIGEGENLDLPYGLERAIQRMEKGEHSIVYLKPSYAFGSVGKEKFQIPPNAELKYELHLKSFEKAKESWEMNSEEKLEQSTIVKERGTVYFKEGKYKQALLQYKKIVSWLEYESSFSNEEAQKAQALRLASHLNLAMCHLKLQAFSAAIESCNKALELDSNNEKGLFRRGEAHLAVNDFELARADFQKVLQLYPNNKAAKTQLAVCQQRIRRQLAREKKLYANMFERLAEEENKAKAEASSGDHPTDTEMKEEQKSNTAGSQSQVETEA | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 26 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 78 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 115 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 118 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 143 | UniProt | Phosphothreonine; by CK2 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 217 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 220 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 220 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 229 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 258 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 263 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 282 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 336 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 350 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 373 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 411 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 430 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 431 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 436 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 436 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 441 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 446 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 448 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 451 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 451 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 453 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 453 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation by CK2 results in loss of HSP90 binding activity.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Widely expressed.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (By similarity).
Interacts with GLMN (PubMed:12604780).
Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU (By similarity).
Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca2+ dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus.
Interacts with GLMN (PubMed:12604780).
Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU (By similarity).
Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca2+ dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q02790 | AGO2 Q9UKV8 | 2 | EBI-1047444, EBI-528269 | |
BINARY | Q02790 | AR P10275 | 2 | EBI-1047444, EBI-608057 | |
BINARY | Q02790 | CDC37 Q16543 | 3 | EBI-1047444, EBI-295634 | |
BINARY | Q02790 | GLMN Q92990 | 5 | EBI-1047444, EBI-726150 | |
BINARY | Q02790 | HSP90AA1 P07900 | 9 | EBI-1047444, EBI-296047 | |
BINARY | Q02790 | HSP90AB1 P08238 | 6 | EBI-1047444, EBI-352572 | |
BINARY | Q02790 | HSPB1 P04792 | 2 | EBI-1047444, EBI-352682 | |
BINARY | Q02790 | MAPT P10636-8 | 7 | EBI-1047444, EBI-366233 | |
XENO | Q02790 | S100a1 P35467 | 7 | EBI-1047444, EBI-6477109 | |
BINARY | Q02790 | S100A2 P29034 | 3 | EBI-1047444, EBI-752230 | |
BINARY | Q02790 | S100A6 P06703 | 3 | EBI-1047444, EBI-352877 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, repeat, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MTAEEMKATESGAQSAPLPMEGVD | ||||||
Domain | 50-138 | PPIase FKBP-type 1 | ||||
Sequence: GDRVFVHYTGWLLDGTKFDSSLDRKDKFSFDLGKGEVIKAWDIAIATMKVGEVCHITCKPEYAYGSAGSPPKIPPNATLVFEVELFEFK | ||||||
Domain | 167-253 | PPIase FKBP-type 2 | ||||
Sequence: GAIVEVALEGYYKDKLFDQRELRFEIGEGENLDLPYGLERAIQRMEKGEHSIVYLKPSYAFGSVGKEKFQIPPNAELKYELHLKSFE | ||||||
Region | 267-400 | Interaction with tubulin | ||||
Sequence: LEQSTIVKERGTVYFKEGKYKQALLQYKKIVSWLEYESSFSNEEAQKAQALRLASHLNLAMCHLKLQAFSAAIESCNKALELDSNNEKGLFRRGEAHLAVNDFELARADFQKVLQLYPNNKAAKTQLAVCQQRI | ||||||
Repeat | 270-303 | TPR 1 | ||||
Sequence: STIVKERGTVYFKEGKYKQALLQYKKIVSWLEYE | ||||||
Repeat | 319-352 | TPR 2 | ||||
Sequence: LASHLNLAMCHLKLQAFSAAIESCNKALELDSNN | ||||||
Repeat | 353-386 | TPR 3 | ||||
Sequence: EKGLFRRGEAHLAVNDFELARADFQKVLQLYPNN | ||||||
Compositional bias | 421-444 | Basic and acidic residues | ||||
Sequence: EENKAKAEASSGDHPTDTEMKEEQ | ||||||
Region | 421-459 | Disordered | ||||
Sequence: EENKAKAEASSGDHPTDTEMKEEQKSNTAGSQSQVETEA | ||||||
Compositional bias | 445-459 | Polar residues | ||||
Sequence: KSNTAGSQSQVETEA |
Domain
The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA).
The C-terminal region (AA 375-458) is required to prevent tubulin polymerization.
The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400.
The TPR repeats mediate mitochondrial localization.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length459
- Mass (Da)51,805
- Last updated2007-01-23 v3
- Checksum6A498105418D9435
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 421-444 | Basic and acidic residues | ||||
Sequence: EENKAKAEASSGDHPTDTEMKEEQ | ||||||
Compositional bias | 445-459 | Polar residues | ||||
Sequence: KSNTAGSQSQVETEA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M88279 EMBL· GenBank· DDBJ | AAA36111.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005841 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471116 EMBL· GenBank· DDBJ | EAW88889.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471116 EMBL· GenBank· DDBJ | EAW88890.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001786 EMBL· GenBank· DDBJ | AAH01786.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007924 EMBL· GenBank· DDBJ | AAH07924.1 EMBL· GenBank· DDBJ | mRNA |